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Updated: Jun 9, 2025
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
IL-33-Pretreated Mesenchymal Stem Cells Attenuate Acute Liver Failure by Improving Homing and Polarizing M2
Hui Yuan1, Yuwen Li2, Zihao Kong3
1Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Mesenchymal stem cells (MSCs) are highly effective in the treatment of acute liver failure (ALF). The efficacy of MSCs is closely related to the inflammatory environment. Therefore, we investigated the functional changes of MSCs in response to interleukin-33 (IL-33) stimulation. The results showed that bone marrow mesenchymal stem cells (BMSCs) pretreated with IL-33 had increased CCR2 expression, targeted CCL2 in the injured liver tissue, and improved the migration ability. Under LPS stimulation, the NF-κB pathway of BMDM was activated, and its phenotype polarized to the M1-type, while BMSCs pretreated with IL-33 inhibited the NF-κB pathway and enhanced M2 macrophage polarization. The M2-type macrophages could further inhibit hepatocytes inflammation, reduce hepatocytes apoptosis, and promote hepatocytes repair. These results suggest that IL-33 can enhance the efficacy of BMSCs in ALF and provide a new strategy for cell therapy of liver diseases.
Insights
Interleukin-33 (IL-33) enhances mesenchymal stem cells (MSCs) for acute liver failure (ALF) treatment. IL-33 pre-treatment improves MSC migration and promotes anti-inflammatory M2 macrophage polarization, aiding liver repair.
Area of Science:
- Immunology and Regenerative Medicine
- Hepatology and Cell Therapy
Background:
- Mesenchymal stem cells (MSCs) show promise in treating acute liver failure (ALF).
- MSC efficacy in ALF is influenced by the liver's inflammatory microenvironment.
Purpose of the Study:
- To investigate the functional modifications of MSCs when stimulated with interleukin-33 (IL-33).
- To evaluate IL-33's potential to enhance MSC-based therapy for ALF.
Main Methods:
- Bone marrow mesenchymal stem cells (BMSCs) were pretreated with IL-33.
- Changes in CCR2 expression and migration ability were assessed.
- Effects on lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and hepatocyte inflammation/apoptosis were analyzed.
Main Results:
- IL-33 pretreatment increased BMSC CCR2 expression and migration.
- IL-33-treated BMSCs inhibited NF-κB activation and promoted M2 macrophage polarization.
- M2 macrophages reduced hepatocyte inflammation and apoptosis, promoting repair.
Conclusions:
- IL-33 enhances the therapeutic efficacy of BMSCs in ALF models.
- This study presents a novel strategy for improving cell therapy in liver diseases.
